The aim of this project is to study the human T lymphotropic virus type-I (HTLV-I) origin and evolution, and its pathogenetic role in tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). To study the origin, evolution and HTLV-I dissemination in the world, we analyzed viral sequences from ex vivo samples of infected individuals, whose origin, clinical diagnosis and general background were known. Using this approach, we were able to identify a novel HTLV-I variant in the southwestern Pacific Islands and formally prove that HTLV-I was disseminated in the New World through slave trade events. We extended our genetic studies to the close HTLV-I relatives (simian T cell leukemia virus) which are found in naturally infected monkeys. We are still investigating the pathogenetic role of HTLV-I in TSP/HAM from different angles: 1) by studying which viral genes are expressed in the cells of infected patients. For example, in this study we identify novel HTLV-I spliced messenger ribonucleic acids; and 2) novel proteins by developing an animal model (rabbits first and perhaps monkeys later) for TSP/HAM using field viral isolates from patients rather than culture adapted HTLV-I.